Usual Adult Dose for Acute Nonlymphocytic Leukemia

• INDUCTION THERAPY: 12 mg/m2 IV daily on days 1 to 3 (in combination with cytarabine at 100 mg/m2 given as a continuous 24-hour IV infusion on days 1 to 7)
• SECOND INDUCTION THERAPY (if needed in the event of an incomplete antileukemic response to the first induction): 12 mg/m2 IV daily on days 1 and 2 (in combination with cytarabine given as a continuous 24-hour IV infusion on days 1 to 5)
• CONSOLIDATION THERAPY: 12 mg/m2 given IV daily on days 1 and 2 (in combination with cytarabine given as a continuous 24-hour IV infusion on days 1 to 5). The first course is given approximately 6 weeks after the final induction course and the second is generally administered 4 weeks after the first.

Comments:

• The IV infusion should be given over 5 to 15 minutes.
• Most complete remissions from ANLL occur during initial induction therapy. In the event of an incomplete antileukemic response, a second induction course may be administered.
• Second inductions should be withheld until severe or life-threatening nonhematologic toxicity associated with the first induction dose is cleared.

Use: For the initial therapy of acute nonlymphocytic leukemia (ANLL) in adults (includes myelogenous, promyelocytic, monocytic, and erythroid acute leukemias) in combination with other approved drug(s)

Usual Adult Dose for Multiple Sclerosis

12 mg/m2 given as a short (approximately 5 to 15 minute) IV infusion every 3 months

Comments:

• The IV infusion should be given over 5 to 15 minutes.
• Evaluation of left ventricular ejection fraction (LVEF) by echocardiogram or multiple gated acquisition (MUGA) scan is recommended prior to all doses.
• LVEF evaluations are recommended if signs of congestive heart failure develop.
• This drug should not be administered to MS patients who have received a cumulative lifetime dose of 140 mg/m2 or more, or those with either an LVEF less than 50% or a clinically significant reduction in LVEF.
• Complete blood counts, including platelets, should be monitored prior to each dose and if signs of infection develop.
• This drug should not be administered to MS patients with neutrophil counts less than 1500 cells/mm3.
• Liver function tests should also be monitored prior to each dose. Use of this drug in MS abnormal liver function tests is not recommended.
• Women who are capable of becoming pregnant (even if they are using birth control) should have a pregnancy test before each dose.

Use: To reduce neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses)

Usual Adult Dose for Prostate Cancer

12 to 14 mg/m2 given as a short IV infusion every 21 days (in combination with corticosteroids)

Comment:

• The IV infusion should be given over 5 to 15 minutes.

Use: Indicated as initial chemotherapy for the treatment of patients with pain related to advanced hormone-refractory prostate cancer in combination with corticosteroids

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Patients with multiple sclerosis who have liver dysfunction should ordinarily not be treated with mitoxantrone (the drug may be administered with caution to other patients with liver dysfunction).

Precautions

US BOXED WARNINGS:

• This drug should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents.
• This drug should be given slowly into a freely flowing IV infusion. It should never be given subcutaneously, IM, or intra-arterially. Severe local tissue damage may occur if there is extravasation during administration.
• NOT FOR INTRATHECAL USE. Severe injury with permanent sequelae can result from intrathecal administration.
• Except for the treatment of acute nonlymphocytic leukemia, this drug generally should not be given to patients with baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving this drug.
• Cardiotoxicity: Congestive heart failure (CHF), potentially fatal, may occur either during therapy or months to years after termination of therapy. The risk increases with cumulative dose and may occur whether or not cardiac risk factors are present. Presence or history of cardiovascular disease, radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or use of other cardiotoxic drugs may increase this risk. In cancer patients, the risk of symptomatic CHF was estimated to be 2.6% for patients receiving up to a cumulative dose of 140 mg/m2. To mitigate the cardiotoxicity risk, prescribers should consider the following:
• ALL PATIENTS: All patients should be assessed for cardiac signs and symptoms by history, physical examination, and ECG prior to starting therapy. All patients should have baseline quantitative evaluation of left ventricular ejection fraction (LVEF) using appropriate methodology (e.g., echocardiogram, multi-gated radionuclide angiography (MUGA), MRI).
• MULTIPLE SCLEROSIS PATIENTS: MS patients with a baseline LVEF below the lower limit of normal should not be treated with this drug. MS patients should be assessed for cardiac signs and symptoms by history, physical examination and ECG prior to each dose. MS patients should undergo quantitative reevaluation of LVEF prior to each dose using the same methodology that was used to assess baseline LVEF. Additional doses of mitoxantrone should not be administered to multiple sclerosis patients who have experienced either a drop in LVEF to below the lower limit of normal or a clinically significant reduction in LVEF during therapy. MS patients should not receive a cumulative mitoxantrone dose greater than 140 mg/m2. MS patients should undergo yearly quantitative LVEF evaluation after stopping therapy to monitor for late occurring cardiotoxicity.
• SECONDARY LEUKEMIA: Therapy in patients with MS and in patients with cancer increases the risk of developing secondary acute myeloid leukemia.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

• This drug is extensively tissue bound and it is unlikely that the therapeutic effect or toxicity would be mitigated by peritoneal or hemodialysis.

Other Comments

Limitations of use:

• This drug is not indicated for the treatment of patients with primary progressive multiple sclerosis.

Patient advice:

• Patients should be informed of the availability of a Medication Guide and instructed to read it prior to initiating treatment and prior to each infusion.
• Patients should be advised that this drug can cause myelosuppression and be informed of signs of myelosuppression.
• Patients should be advised that this drug can cause congestive heart failure that may lead to death, even in people who have never had heart problems before.
• Patients with MS should be advised that they should receive cardiac monitoring prior to each dose and yearly after stopping therapy.
• Patients should be advised that this drug may impart a blue-green color to the urine and/or sclera for 24 hours after administration.